α-sulfin-and α-sulfonamino acid amides

ABSTRACT

The invention relates to α-sulfin- and α-sulfonamino acid amides of the general formula I                    
     including the optical isomers thereof and mixtures of such isomers, 
     wherein 
     n is a number zero or one; 
     R 1  is C 1 -C 12 alkyl, C 1 -C 12 alkyl substituted with C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfonyl, C 3 -C 8 cycloalkyl, cyano, C 1 -C 6 alkoxycarbonyl, C 3 -C 6 alkenyloxycarbonyl or C 3 -C 6 alkynyloxycarbonyl; C 3 -C 8 cycloalkyl; C 2 -C 12 alkenyl; C 2 -C 12 alkynyl; C 1 -C 12 haloalkyl; or a group NR 12 R 13  wherein R 12  and R 13  are each independently of the other hydrogen or C 1 -C 6 -alkyl, or together are tetra- or penta-methylene; 
     R 2  and R 3  are each independently hydrogen; C 1 -C 8 alkyl; C 1 -C 8 alkyl substituted with hydroxy, mercapto, C 1 -C 4 alkoxy or C 1 -C 4 alkylthio; C 3 -C 8 alkenyl; C 3 -C 8 alkynyl; C 3 -C 8 cycloalkyl; C 3 -C 8 cycloalkyl-C 1 -C 4 alkyl; or the two groups R 2  and R 3  together with the carbon atom to which they are bonded form a three- to eight-membered hydrocarbon ring; 
     R 4 , R 5 , R 6  and R 7  are each independently hydrogen or C 1 -C 4 alkyl; 
     R 8  is C 1 -C 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl; 
     R 9  and R 10  are each independently hydrogen or C 1 -C 4 alkyl; and 
     R 11  is either                    
      in wherein 
     R 14 , R, 15 , R 16  and R 17  are each independently hydrogen or C 1 -C 4 alkyl, 
     X is oxygen, sulfur or —NR 18 —, wherein R 18  is hydrogen or C 1 -C 4 alkyl, and 
     A is optionally substituted mono- or polycylic aryl or heteroaryl, and 
     to the preparation of those substances and to agrochemical compositions comprising at least one of those compounds as active ingredient. The invention relates also to the preparation of compositions and to the use of the compounds or of the compositions in controlling or preventing the infestation of plants by phytopathogenic microorganisms, especially fungi.

This application is a continuation of PCT/EP99/09350, filed Dec. 1, 1999.

The present invention relates to novel α-sulfin- and α-sulfonamino acid amides of formula I below. It relates to the preparation of those substances and to agrochemical compositions comprising at least one of those compounds as active ingredient. The invention relates also to the preparation of the said compositions and to the use of the compounds or of the compositions in controlling or preventing the infestation of plants by phytopathogenic microorganisms, especially fungi.

The invention relates to α-sulfin- and α-sulfonamino acid amides of the general formula I

including the optical isomers thereof and mixtures of such isomers,

wherein

n is a number zero or one;

R₁ is C₁-C₁₂alkyl, C₁-C₁₂alkyl substituted with C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl or C₃-C₆alkynyloxycarbonyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl, or together are tetra- or penta-methylene;

R₂ and R₃ are each independently hydrogen; C₁-C₈alkyl; C₁-C₈alkyl substituted with hydroxy, mercapto, C₁-C₄alkoxy or C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl; or the two groups R₂ and R₃ together with the carbon atom to which they are bonded form a three- to eight-membered hydrocarbon ring;

R₄, R₅, R₆ and R₇ are each independently hydrogen or C₁-C₄alkyl;

R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl;

R₉ and R₁₀ are each independently hydrogen or C₁-C₄alkyl; and

R₁₁ is either

 in wherein

R₁₄, R₁₅, R₁₆ and R₁₇ are each independently hydrogen or C₁-C₄alkyl,

X is oxygen, sulfur or —NR₁₈—, wherein R₁₈ is hydrogen or C₁-C₄alkyl, and

A is optionally substituted mono- or polycylic aryl or heteroaryl.

In the above definition aryl includes aromatic hydrocarbon rings like phenyl, naphthyl, anthracenyl, phenanthrenyl, with phenyl being preferred.

Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member. Examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl.

The above aryl and heteroaryl groups may carry one or more identical or different substituents. Normally not more than three substituents are present at the same time. Examples of substituents of aryl or heteroaryl groups are: alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, phenyl and phenyl-alkyl, it being possible in turn for all of the preceding groups to carry one or more identical or different halogen atoms; alkoxy; alkenyloxy; alkynyloxy; alkoxyalkyl; haloalkoxy, alkylthio; haloalkylthio; alkylsulfonyl; formyl; alkanoyl; hydroxy; halogen; cyano; nitro; amino; alkylamino; dialkylamino; carboxy; alkoxycarbonyl; alkenyloxycarbonyl; alkynyloxycarbonyl.

In the above definitions “halogen” includes fluorine, chlorine, bromine and iodine.

The alkyl, alkenyl and alkynyl radicals may be straight-chain or branched. This applies also to the alkyl, alkenyl or alkynyl parts of other alkyl-, alkenyl- or alkynyl-containing groups.

Depending upon the number of carbon atoms mentioned, alkyl on its own or as part of another substituent is to be understood as being, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl and the isomers thereof, for example isopropyl, isobutyl, tert-butyl or sec-butyl, isopentyl or tert-pentyl.

Cycloalkyl is, depending upon the number of carbon atoms mentioned, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl.

Depending upon the number of carbon atoms mentioned, alkenyl as a group or as a structural element of other groups is to be understood as being, for example, ethenyl, allyl, 1-propenyl, buten-2-yl, buten-3-yl, penten-1-yl, penten-3-yl, hexen-1-yl, 4-methyl-3-pentenyl or 4-methyl-3-hexenyl.

Alkynyl as a group or as a structural element of other groups is, for example, ethynyl, propyn-1-yl, propyn-2-yl, butyn-1-yl, butyn-2-yl, 1-methyl-2-butynyl, hexyn-1-yl, 1-ethyl-2-butynyl or octyn-1-yl.

A haloalkyl group may contain one or more (identical or different) halogen atoms, and for example may stand for CHCl₂, CH₂F, CCl₃, CH₂Cl, CHF₂, CF₃, CH₂CH₂Br, C₂C₅, CH₂Br, CHClBr, CF₃CH₂, etc.

Where R₂ and R₃ together with the carbon atom to which they are attached form a hydrocarbon ring the ring corresponds to cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane or cyclooctane

The presence of at least one asymmetric carbon atom and/or at least one asymmetric oxidized sulfur atom in the compounds of formula I means that the compounds may occur in optically isomeric forms. As a result of the presence of a possible aliphatic C═C double bond, geometric isomerism may also occur. Formula I is intended to include all those possible isomeric forms and mixtures thereof.

Preferred subgroups of compounds of formula I are those wherein

n is one; or

R₁ is C₁-C₁₂alkyl, C₁-C₁₂alkyl substituted with C₁-C₄alkoxy, C₁-C₄alkylthio, or C₁-C₄alkylsulfonyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl, or together are tetra- or penta-methylene; or

R₁ is C₁-C₁₂alkyl, C₂-C₁₂alkenyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl; or

R₁ is C₁-C₄alkyl, C₂-C₄alkenyl; C₁-C₄haloalkyl; or C₁-C₂-dialkylamino; or

R₁ is C₁-C₄alkyl, vinyl; C₁-C₄haloalkyl; or dimethylamino; or

R₂ is hydrogen and R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted with hydroxy, mercapto, C₁-C₄alkoxy or C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl; or

R₂ is hydrogen and R₃ is C₁-C₄alkyl; C₃-C₄alkenyl or cyclopropyl; or

R₂ is hydrogen and R₃ is C₃-C₄alkyl; allyl or cyclopropyl; or

R₂ is hydrogen and R₃ is isopropyl; or

R₄ is hydrogen or C₁-C₄alkyl and R₅, R₆ and R₇ are each hydrogen; or

R₄ is hydrogen, methyl or ethyl and R₅, R₆ and R₇ are each hydrogen; or

R₄ is hydrogen or methyl and R₅, R₆ and R₇ are each hydrogen; or

R₄, R₅, R₆ and R₇ are each hydrogen; or

R₈ is C₁-C₆alkyl; or

R₈ is methyl or ethyl; or

R₈ is methyl; or

R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each independently hydrogen or methyl; or

R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each hydrogen; or

X is oxygen, sulfur or —NR₈—, wherein R₁₈ is hydrogen or methyl; or

X is oxygen, sulfur or —NH—; or

X is oxygen; or

A is optionally substituted heteroaryl consisting of one or two five to six membered rings containing one to four identical or different heteroatoms selected from oxygen, nitrogen and sulfur; or

A is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzthiazolyl, benzoxazolyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₃-C₈-cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄-alkyl, phenyl, phenyl-C₁-C₄-alkyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₃-C₈-alkenyloxy; C₃-C₈-alkynyloxy; C₁-C₈-alkoxy-C₁-C₄-alkyl; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; C₁-C₈-alkylsulfonyl; formyl; C₂-C₈-alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈-alkylamino; C₁-C₈-dialkylamino; carboxy; C₁-C₈-alkoxycarbonyl; C₁-C₈-alkenyloxycarbonyl or C₁-C₈-alkynyloxycarbonyl; or

A is phenyl, naphthyl, thienyl, pyridyl, pyrimidinyl, triazinyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl; or

A is phenyl or pyridyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl; C₁-C₈-haloalkyl; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl.

Further preferred subgroups of the compounds of formula I are those wherein

R₁ is C₁-C₁₂alkyl, C₁-C₁₂alkyl substituted with C₁-C₄alkoxy, C₁-C₄alkylthio, or C₁-C₄alkylsulfonyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl, or together are tetra- or penta-methylene; and

R₂ is hydrogen and R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted with hydroxy, mercapto, C₁-C₄alkoxy or C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₁-C₄alkyl; and

R₄ is hydrogen or C₁-C₄alkyl and R₅, R₆ and R₇ are each hydrogen; or those wherein

n is one; and

R₁ is C₁-C₁₂alkyl, C₂-C₁₂alkenyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl; and

R₂ is hydrogen and R₃ is C₁-C₄alkyl; C₃-C₄alkenyl or cyclopropyl; and

R₄ is hydrogen, methyl or ethyl and R₅, R₆ and R₇ are each hydrogen; and

R₈ is C₁-C₆alkyl; or those wherein

n is one; and

R₁ is C₁-C₄alkyl, C₂-C₄alkenyl; C₁-C₄haloalkyl; or C₁-C₂-dialkylamino; and

R₂ is hydrogen and R₃ is C₃-C₄alkyl; allyl or cyclopropyl; and

R₄ is hydrogen or methyl and R₅, R₆ and R₇ are each hydrogen; and

R₈ is methyl or ethyl; or those wherein

n is one; and

R₁ is C₁-C₄alkyl, vinyl; C₁-C₄haloalkyl; or dimethylamino; and

R₂ is hydrogen and R₃ is isopropyl; and

R₄, R₅, R₆ and R₇ are each hydrogen; and

R₈ is methyl.

Amongst the above preferred subgroups of compounds of formula I in turn those are preferred wherein

A is optionally substituted heteroaryl consisting of one or two five to six membered rings containing one to four identical or different heteroatoms selected from oxygen, nitrogen and sulfur; or those wherein

R₉, R₁₀, R₁₄, R₁₆, R₁₇ are each independently hydrogen or methyl; and

X is oxygen, sulfur or —NR₁₈—, wherein R₁₈ is hydrogen or methyl; and

A is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzthiazolyl, benzoxazolyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₃—C₈-cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄-alkyl, phenyl, phenyl-C₁-C₄-alkyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₃-C₈-alkenyloxy; C₃-C₈-alkynyloxy; C₁-C₈-alkoxy-C₁-C₄-alkyl; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; C₁-C₈-alkylsulfonyl; formyl; C₂-C₈-alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈-alkylamino; C₁-C₈-dialkylamino; carboxy; C₁-C₈-alkoxycarbonyl; C₁-C₈-alkenyloxycarbonyl or C₁-C₈-alkynyloxycarbonyl; or those wherein

R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each hydrogen; and

X is oxygen, sulfur or —NH—; or

A is phenyl, naphthyl, thienyl, pyridyl, pyrimidinyl, triazinyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl; or those wherein

R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each hydrogen; and

X is oxygen; and

A is phenyl or pyridyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl; C₁-C₈-haloalkyl; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl.

Preferred individual compounds are:

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-dimethylaminosulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-pentanoylamide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-phenoxy-ethoxy]-3-methoxy-phenyl}-ethyl)-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(3-methyl-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-methyl-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(3-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(2-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[1-methyl-2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(3,4-dichloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(3-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-chloro-phenylthio)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[1-methyl-2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[3-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-2-cyclopropyl-acetamide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(2-fluoro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(2-fluoro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-bromo-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)(E)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)(Z)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-butyramide,

(S)-2-ethanesulfonylamino-N-(2-{4-[2-(4-chloro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-pentanoylamide,

Z-(S)-2-methanesulfonylamino-N-(2-{4-[2-(4-chloro-phenoxy)-allyloxy]-3-methoxy-phenyl}-ethyl)-pentanoylamide, and

Z-(S)-2-ethanesulfonylamino-N-(2-{4-[3-phenoxy-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide.

Certain α-sulfin- and α-sulfonamino acid derivatives having a different kind of structure have already been proposed for controlling plant-destructive fungi (for example in WO 95/030651, WO 97/14677, WO 98/38160 and WO 98/38161). The action of those preparations is not, however, satisfactory in all aspects of agricultural needs. Surprisingly, with the compound structure of formula I, new kinds of microbicides having a high level of activity have been found.

The α-sulfin- and α-sulfonamino acid amides of formula I may be obtained according to one of the following processes:

a)

An amino acid of formula II or a carboxy-activated derivative of an amino acid of formula II wherein R₁, n, R₂ and R₃ are as defined for formula I is reacted with an amine of formula III wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined above optionally in the presence of a base and optionally in the presence of a diluting agent (step B).

Carboxy-activated derivatives of the amino acid of formula II encompasses all compounds having an activated carboxyl group like an acid halide, such as an acid chloride, like symmetrical or mixed anhydrides, such as mixed anhydrides with O-alkylcarbonates, like activated esters, such as p-nitrophenylesters or N-hydroxysucinimidesters, as well as in situ produced activated forms of the amino acid of formula II by condensating agents, such as dicyclohexylcarbodiimid, carbonyidiimidazol, benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate, O-benzotriazol-1-yl N,N,N′,N′-bis(pentamethylene)-uronium hexafluorophosphate, O-benzotriazol-1-yl N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate, O-benzotriazol-1-yl N,N,N′,N′-tetramethyluronium hexafluoro-phosphate or benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate. The mixed anhydrides of the amino acids of the formula II may be prepared by reaction of an amirnio acid of formula II with chloroformic acid esters like chloroformic acid alkylesters, such as ethyl chloroformate or isobutyl chloroformate, optionally in the presence of an organic or inorganic base like a tertiary amine, such as triethylamine, N,N-diisopropyl-ethylamine, pyridine, n-methyl-piperidine or N-methyl-morpholin.

The present reaction is preferably performed in an inert solvent like aromatic, non-aromatic or halogenated hydrocarbons, such as chlorohydrocarbons e.g. dichloromethane or toluene; ketones, e.g. acetone; esters, e.g. ethyl acetate; amides, e.g. N,N-dimethylformamide; nitrites e.g. acetonitrile; or ethers e.g. diethylether, tert-butyl-methylether, dioxane or tetrahydrofurane or water. It is also possible to use mixtures of these solvents. The reaction is preformed optionally in the presence of an organic or inorganic base like a tertiary amine, e.g. triethylamine, N,N-diisopropyl-ethylamine, pyridine, n-methyl-piperidine or N-methyl-morpholin, like a metal hydroxide or a metal carbonate, preferentially an alkali hydroxide or an alkali carbonate, such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures ranging from −80° C. to +150° C., preferentially at temperatures ranging from −40° C. to +40° C.

The compounds of formula II may be prepared by reaction of an amino acid of formula IV where R₂ and R₃ are as defined for formula I with a sulfonyl halide or a sulfinyl halide of formula V where R₁ and n have the same meanings as defined above and where X is halide, preferentially chlorine or bromine (step A).

The reaction may be performed in an inert solvent like aromatic, non-aromatic or halogenated hydrocarbons, such as chlorohydrocarbons, e.g. dichloromethane or toluene; ketones, e.g. acetone; esters, e.g. ethyl acetate; ethers, e.g. diethylether, tert-butyl-methylether, dioxane or tetrahydrofurane or water. It is also possible to use mixtures of these solvents. The reaction is performed optionally in the presence of an organic or inorganic base like a tertiary amine, such as triethylamine, N,N-diisopropyl-ethylamine, pyridine, n-methyl-piperidine or N-methyl-morpholine, like a metal hydroxide or a metal carbonate, preferentially an alkali hydroxide or an alkali carbonate, such as lithium hydroxide, sodium hydroxide or potassium hydroxide at temperatures ranging from −80° C. to +150° C., preferentially at temperatures ranging from −40° C. to +40° C.

b)

The compounds of formula I may also be prepared by reaction of an amino acid derivative of formula VI wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined for formula I with a sulfonyl halide or a sulfinyl halide of formula V wherein R₁ and n are as defined for formula I and X is halide, preferentially chlorine or bromine (step C). The reaction is performed in the same manner as described for step A.

c)

The compounds of formula I may also be prepared by reaction of a phenol of formula VII wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ are as defined for formula I with a compound of formula VIII wherein R₉, R₁₀ and R₁₁ are as defined for formula I and Y is a leaving group like a halide such as a chloride or bromide or a sulfonic ester such as a tosylate, mesylate or triflate (step D).

The reaction may be performed in an inert solvent like aromatic, non-aromatic or halogenated hydrocarbons, such as chlorohydrocarbons e.g. dichloromethane or toluene; ketones e.g. acetone or 2-butanone; esters, e.g. ethyl acetate; ethers, e.g. diethylether, tert-butyl-methylether, dioxane or tetrahydrofurane, amides, e.g. dimethylformamide, nitrites, e.g. acetonitrile, alcohols, e.g. methanol, ethanol, isopropanol, n-butanol or tert-butanol, sulfoxides e.g. dimethylsulfoxide or water. It is also possible to use mixtures of these solvents. The reaction is performed optionally in the presence of an organic or inorganic base like a tertiary amine, such as triethylamine, N,N-diisopropyl-ethylamine, pyridine, N-methyl-piperidine or N-methyl-morpholine, like a metal hydroxide, a metal carbonate or a metal alkoxide, preferentially an alkali hydroxide, an alkali carbonate or an alkali alkoxide, such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide or potassium tert-butoxide at temperatures ranging from −80° C. to +200° C., preferentially at temperatures ranging from 0° C. to +120° C.

d)

The compounds of formula Ia may also be prepared via formula IX wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇, R₈ and A are defined for formula I by reacting of a phenol of formula VII wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇ and R8 are as defined for formula I with a compound of formula VIIIa wherein R₉, R₁₀ and A are as defined for formula I and Y is a leaving group like a halide such as a chloride or bromide or a sulfonic ester such as a tosylate, mesylate or triflate (step E).

The reaction is performed in the same manner as described for step D.

The compounds of formula la where R₁₁ is (E) —CH═CH—A and A is as defined for formula I may be prepared by reaction of compounds of formula IX with hydrogen.

The reaction is performed in a solvent like ethers, e.g. diethylether, dioxane or tetrahydrofuran, or like alcohols, e.g. methanol or ethanol, or water in the presence of transition metals or transition metal salts, e.g. nickel, cobalt, palladium, platinium or rhodium, optionally in the presence of bases, e.g. ammonia, or in the presence of salts, e.g. barium sulfate, at temperatures ranging from −20° C. to +160° C. and at pressures ranging from 1 to 200 bar.

aa) The intermediate amines of formula III may be obtained by one of the following processes:

Step 1 is the alkylation of a phenol with a compound of formula VIII. The reaction is performed in the same manner as described for procedure c).

Step 2 is the reaction of an aromatic aldehyde with nitromethane. This reaction is performed in a solvent like an organic carboxylic acids, e.g. acetic acidoptionally in the presence of the ammonium salt of this carboxylic acid, e.g. ammonium acetate at temperatures ranging from 0° C. to +200° C.

Step 3 is the reduction of an unsaturated nitrogen-compound. This reaction is performed in a solvent like an ether, e.g. diethylether, dioxane or tetrahydrofuran, or an alcohol, e.g. methanol, ethanol or isopropanol, with borohydride, with a boron-complex, e.g. the complex of borohydride with tetrahyrofuran, with an alkaliborohydride, with an alkalialuminiumhydride, e.g. lithiumaluminiumhydride, with aluminiumhydride, with an aluminiumalkoxyhydride or with hydrogen optionally in the presence of a transition metal, a transition metal salt or a transition metal complex, e.g. nickel, cobalt, palladium, platinium or rhodium at temperatures ranging from −50° C. to +200° C.

Step 4 is the reaction of an aldehyde or a ketone of formula with hydroxylamine or with a salt of hydroxylamine. This reaction is performed in a solvent like an alcohol, e.g. methanol, ethanol or isopropanol, like an ether, e.g. diethylether, dioxane or tetrahydrofuran, like an amide, e.g. dimethylformamide, or in water or in a mixture of these solvents optionally in the presence of an organic or inorganic base like a tertiary amine, e.g. triethylamine, like a heterocyclic compound containing nitrogen, e.g. pyridine, or like an alkalicarbonate, e.g. sodium carbonate or potassium carbonate, at temperatures ranging from −20° C. to +150° C.

Step 5 is the exchange of hydroxy by cyanide. This reaction is performed in an organic solvent like an amide, e.g. dimethylformamide using a metal cyanide like an alkali cyanide, e.g. sodium cyanide or potassium cyanide, at temperatures ranging from 0° C. to +200° C.

Step 6 is the hydrolysis of an alkyl ester. This reaction is performed in a solvent like an alcohol, e.g. methanol, ethanol or isopropanol, like an ether, e.g. diethylether, dioxane or tetrahydrofuran, like a halogenated hydrocarbon, e.g. dichloromethane, or water or in a mixture of these solvents optionally in the presence of an alkali hydroxide, e.g. lithium hydroxide, sodium hydroxide or potassium hydroxide, or optionally in the presence of an acid, e.g. hydrogen chloride, sulfuric acid or trifluoroacetic acid at temperatures ranging from −20° C. to +160° C.

Step 7 is the reaction of a carboxylic acid or the activated form of this carboxylic acid with hydrogen azide or an azide-salt. An activated form of a carboxylic acid can be the acid halogenide, e.g. acid chloride, a symmetric or a mixed anhydride. Azide-salts can be alkali azides, e.g. sodium azide. The reaction is performed in a solvent like a hydrocarbon, e.g. toluene or xylene, like a halogenated hydrocarbon, e.g. chloroform, like an ether, e.g. dioxane, like a ketone, e.g. acetone or 2-butanone, like an alcohol, e.g. methanol, ethanol or tert-butanol, or water or in a mixture of these solvents optionally in the presence of an acid like an inorganic acid, e.g. sulfuric acid or hydrogen chloride at temperatures ranging from −40° C. to +200° C.

In a preferred form the compounds of formula XXVI are prepared starting from compounds of the formula XXV by applying step 5 and step 1 in the same pot.

bb) Amines of formula VI can be obtained by the following process:

Step 8 is the amidation of an BOC protected amino acid of formula XXI with an amine of formula XXII. The reaction is performed in the same manner as described for step A.

Step 9 is the alkylation of a phenol of formula XXIlII with an compound of formula VIII. The reaction is performed in the same manner as described for step D.

Step 10 is the hydrolysis of a carbamate of formula XIX. The reaction is performed in a solvent like hydrocarbons, e.g. toluene, like halogenated hydrocarbons, e.g. dichloromethane, like ketones, e.g. acetone, like esters, e.g. ethyl acetate, like ethers, e.g. dioxane or tetrahydrofuran, or like water or in mixtures of these solvents optionally in the presence of an organic acid like carboxylic acid, e.g. trifluoroacetic acid, or like a sulfonic acid, e.g. methanesulfonic acid or toluenesulfonic acid, or in the presence of an inorganic acid, e.g. hydrogen chloride or sulfuric acid, at temperatures ranging from −40° C. to +160° C.

The compounds of formula I are oils or solids at room temperature and are distinguished by valuable microbicidal properties. They can be used in the agricultural sector or related fields preventively and curatively in the control of plant-destructive microorganisms. The compounds of formula I according to the invention are distinguished at low rates of concentration not only by outstanding microbicidal, especially fungicidal, activity but also by being especially well tolerated by plants.

Surprisingly, it has now been found that the compounds of formula I have for practical purposes a very advantageous biocidal spectrum in the control of phytopathogenic micro-organisms, especially fungi. They possess very advantageous curative and preventive properties and are used in the protection of numerous crop plants. With the compounds of formula I it is possible to inhibit or destroy phytopathogenic microorganisms that occur on various crops of useful plants or on parts of such plants (fruit, blossom, leaves, stems, tubers, roots), while parts of the plants which grow later also remain protected, for example, against phytopathogenic fungi.

The novel compounds of formula I prove to be effective against specific genera of the fungus class Fungi imperfecti (e.g. Cercospora), Basidiomycetes (e.g. Puccinia) and Ascomycetes (e.g. Erysiphe and Venturia) and especially against Oomycetes (e.g. Plasmopara, Peronospora, Pythium and Phytophthora). They therefore represent in plant protection a valuable addition to the compositions for controlling phytopathogenic fungi. The compounds of formula I can also be used as dressings for protecting seed (fruit, tubers, grains) and plant cuttings from fungal infections and against phytopathogenic fungi that occur in the soil.

The invention relates also to compositions comprising compounds of formula I as active ingredient, especially plant-protecting compositions, and to the use thereof in the agricultural sector or related fields.

In addition, the present invention includes the preparation of those compositions, wherein the active ingredient is homogeneously mixed with one or more of the substances or groups of substances described herein. Also included is a method of treating plants which is distinguished by the application of the novel compounds of formula I or of the novel compositions.

Target crops to be protected within the scope of this invention comprise, for example, the following species of plants: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, stone fruit and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucurbitaceae (marrows, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamon, camphor) and plants such as tobacco, nuts, coffee, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, and also ornamentals.

The compounds of formula I are normally used in the form of compositions and can be applied to the area or plant to be treated simultaneously or in succession with other active ingredients. Those other active ingredients may be fertilisers, micronutrient donors or other preparations that influence plant growth. It is also possible to use selective herbicides or insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of those preparations, if desired together with further carriers, surfactants or other application-promoting adjuvants customarily employed in formulation technology.

The compounds of formula I can be mixed with other fungicides, resulting in some cases in unexpected synergistic activities.

Mixing components which are particularly preferred are azoles such as azaconazole, bitertanol, propiconazole, difenoconazole, diniconazole, cyproconazole, epoxiconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole, tetraconazole, fenbuconazole, metconazole, myclobutanil, perfurazoate, penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon, triadimenol, triflumizole or triticonazole; pyrimidinyl carbinoles such as ancymidol, fenarimol or nuarimol; 2-amino-pyrirridine such as bupirimate, dimethirimol or ethirimol; morpholines such as dodemorph, fenpropidin, fenpropimorph, spiroxamin or tridemorph; anilinopyrimidines such as cyprodinil, pyrimethanil or mepanipyrim; pyrroles such as fenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace or oxadixyl; benzimidazoles such as benomyl, carbendazim, debacarb, fuberidazole or thiabendazole; dicarboximides such as chlozolinate, dichlozoline, iprodine, myclozoline, procymidone or vinclozolin; carboxamides such as carboxin, fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidines such as guazatine, dodine or iminoctadine; strobilurines such as azoxystrobin, kresoxim-methyl, metominostrobin, SSF-129, methyl 2-[(2-trifluoromethyl)-pyrid-6-yloxymethyl]-3-methoxyacrylate or 2-[α{[(α-methyl-3-trifluoromethyl-benzyl)imino]-oxy}-o-tolyl]-glyoxylic acid-methylester-O-methyloxime; dithiocarbamates such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb or ziram; N-halomethylthio-dicarboximides such as captafol, captan, dichlofluanid, fluoromide, folpet or tolyfluanid; copper compounds such as Bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, mancopper or oxine-copper; nitrophenol derivatives such as dinocap or nitrothal-isopropyl; organo phosphorous derivatives such as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos or toclofos-methyl; and other compounds of diverse structures such as acibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran, diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone, fenamidone, fentin, ferimzone, fluazinam, flusulfamide, fenhexamid, fosetyl-aluminium, hymexazol, kasugamycin, methasulfocarb, pencycuron, phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforine or validamycin.

Suitable carriers and surfactants may be solid or liquid and correspond to the substances ordinarily employed in formulation technology, such as e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilisers. Such carriers and additives are described, for example, in WO 95/30651.

A preferred method of applying a compound of formula I, or an agrochemical composition comprising at least one of those compounds, is application to the foliage (foliar application), the frequency and the rate of application depending upon the risk of infestation by the pathogen in question. The compounds of formula I may also be applied to seed grains (coating) either by impregnating the grains with a liquid formulation of the active ingredient or by coating them with a solid formulation.

The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in formulation technology, and are for that purpose advantageously formulated in known manner e.g. into emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules, and by encapsulation in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances.

Advantageous rates of application are normally from 1 g to 2 kg of active ingredient (a.i.) per hectare (ha), preferably from 10 g to 1 kg a.i./ha, especially from 25 g to 750 g a.i./ha. When used as seed dressings, rates of from 0.001 g to 1.0 g of active ingredient per kg of seed are advantageously used.

The formulations, i.e. the compositions, preparations or mixtures comprising the compound(s) (active ingredient(s)) of formula I and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredient with extenders, e.g. solvents, solid carriers and, where appropriate, surface-active compounds (surfactants).

Further surfactants customarily used in formulation technology will be known to the person skilled in the art or can be found in the relevant technical literature.

The agrochemical compositions usually comprise 0.01 to 99% by weight, preferably 0.1 to 95% by weight, of a compound of formula I, 99.99 to 1% by weight, preferably 99.9 to 5% by weight, of a solid or liquid adjuvant, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.

Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.

The compositions may also comprise further ingredients, such as stabilisers, antifoams, viscosity regulators, binders and tackifiers, as well as fertilisers or other active ingredients for obtaining special effects.

The Examples which follow illustrate the invention described above, without limiting the scope thereof in any way. Temperatures are given in degrees Celsius.

Preparation Examples for Compounds of Formula I

EXAMPLE A1.1 (S)-2-Ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide

To a mixture of (S)-2-ethanesulfonylamino-3-methyl-butyric acid (0.63 g), 2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine hydrochloride (1.0 g) and diethyl-isopropylamine (1.8 ml) in dimethylformamide (30 ml) is added benzotriazol-1-yloxy-tris-(dimethylamino)phosphonium hexafluorophosphate (1.5 g) in one portion. The reaction mixture is stirred for 2 hours at room temperature. Water (200 ml) is then added. The mixture is extracted with ethyl acetate (2×200 ml). The organic layers are washed with brine (2×200 ml), dried (MgSO₄) and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 2:1) and recrystallisation (ethyl acetate/hexane). (S)-2-Ethanesulfonylamino-N-(2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide is obtained, m.p. 124-125° C.

Analogously to example A1.1 the compounds listed in table A1 are obtained.

TABLE A1

No. R₁ R₃ *⁾ CR₉R₁₀R₁₁ Data^(a), b)) A1.01 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(4-F—Ph) 124-125^(a)) A1.02 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(4-F—Ph) 124-126^(a)) A1.03 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(4-F—Ph) 122-124^(a)) A1.04 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(4-F—Ph) 132-133^(a)) A1.05 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(4-F—Ph) 113-115^(a)) A1.06 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—Ph 112-113^(a)) A1.07 CH₃ C₃H₇-i (S) —(CH₂)₂—O—Ph 120-123^(a)) A1.08 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—Ph 112-114^(a)) A1.09 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—Ph 109-110^(a)) A1.10 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—Ph 131-132^(a)) A1.11 C₂H₅ —CH₂—CH═CH₂ (R,S) —(CH₂)₂—O—(4-F—Ph) 115-118^(a)) A1.12 C₂H₅ —CH₂—CH═CH₂ (R,S) —(CH₂)₂—O—Ph 118-119^(a)) A1.13 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(4-Cl—Ph) 120-122^(a)) A1.14 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(4-Cl—Ph) 122-123^(a)) A1.15 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(4-Cl—Ph) 114-116^(a)) A1.16 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(4-Cl—Ph) 132-134^(a)) A1.17 CH₂═C(CH₃)—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(4-F—Ph) 109-112^(a)) A1.18 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(4-F—Ph) 120-123^(a)) A1.19 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(4-F—Ph) 147-150^(a)) A1.20 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(4-Cl—Ph) 150-152^(a)) A1.21 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(2-Cl—Ph) 134-135^(a)) A1.22 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 146-147^(a)) A1.23 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) resin, 495^(c)) A1.24 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 135-138^(a)) A1.25 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 117-118^(a)) A1.26 C₂H₅ C₃H₇-i (S) —(CH₂)₂—S—(4-Cl—Ph) 128-129^(a)) A1.27 C₂H₅ C₃H₇-i (S) —(CH₂)₂—S—Ph resin, 493^(c)) A1.28 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(4-Br—Ph) 543^(b)) A1.29 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(4-Br—Ph) 557^(b)) A1.30 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(4-Br—Ph) 571^(b)) A1.31 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(4-Br—Ph) 605^(b)) A1.32 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(4-Br—Ph) 571^(b)) A1.33 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(4-Br—Ph) 543^(b)) A1.34 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(4-Br—Ph) 557^(b)) A1.35 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(2-Br—Ph) 543^(b)) A1.36 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(2-Br—Ph) 557^(b)) A1.37 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(2-Br—Ph) 571^(b)) A1.38 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(2-Br—Ph) 605^(b)) A1.39 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(2-Br—Ph) 571^(b)) A1.40 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(2-Br—Ph) 543^(b)) A1.41 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(2-Br—Ph) 557^(b)) A1.42 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(2-Cl—Ph) 527^(b)) A1.43 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(2-Cl—Ph) 499^(b)) A1.44 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(2-Cl—Ph) 513^(b)) A1.45 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 479^(b)) A1.46 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 493^(b)) A1.47 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 507^(b)) A1.48 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 541^(b)) A1.49 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(4-CH₃—Ph) 479^(b)) A1.50 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(4-CH₃—Ph) 493^(b)) A1.51 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 493^(b)) A1.52 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 507^(b)) A1.53 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 541^(b)) A1.54 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(3-CH₃—Ph) 507^(b)) A1.55 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(3-CH₃—Ph) 479^(b)) A1.56 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(3-CH₃—Ph) 493^(b)) A1.57 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) 497^(b)) A1.58 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) 511^(b)) A1.59 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(3-F—Ph) 483^(b)) A1.60 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(3-F—Ph) 497^(b)) A1.61 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 561^(b)) A1.62 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 595^(b)) A1.63 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 561^(b)) A1.64 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 533^(b)) A1.65 C₂H₅ C₃H₇-n (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 547^(b)) A1.66 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 529^(b)) A1.67 C₃H₇-n C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 543^(b)) A1.68 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(2-naphthyl) 543^(b)) A1.69 C₂H₅ C₂H₅ (S) —(CH₂)₂—O—(2-naphthyl) 515^(b)) A1.70 C₂H₅ C₃H₇-i (S) —(CH₂)₂—N(C₂H₅)—Ph 108-110^(a)) A1.71 C₂H₅ C₃H₇-i (S) —(CH₂)₂—N(CH₃)—Ph 106-107^(a)) A1.72 C₂H₅ C₃H₇-i (S) —CH(CH₃)—CH₂—O—(4-Cl—Ph) resin, 525^(c)) A1.73 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(2-Cl—Ph) 132-133^(a)) A1.74 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 147-148^(a)) A1.75 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 143-144^(a)) A1.76 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) 113-115^(a)) A1.77 CH₃ C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 116-117^(a)) A1.78 CH₃ C₃H₇-i (S) —(CH₂)₂—S—(4-Cl—Ph) resin, 513^(c)) A1.79 CH₃ C₃H₇-i (S) —(CH₂)₂—N(C₂H₅)—Ph 121-122^(a)) A1.80 CH₃ C₃H₇-i (S) —CH(CH₃)—CH₂—O—(4-Cl—Ph) 109-110^(a)) A1.81 CH₃ C₃H₇-i (S) —(CH₂)₂—N(CH₃)—Ph 128-129^(a)) A1.82 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(2-Cl—Ph)  97-100^(a)) A1.83 C₂H₅ C₃H₇-i (S) —(CH₂)₂—O—(3,4-Cl₂—Ph) 129-130^(a)) A1.84 CH₃ C₃H₇-i (S) —(CH₂)₂—S—Ph 124-126^(a)) A1.85 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 149-150^(a)) A1.86 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) 106-109^(a)) A1.87 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(4-CH₃—Ph) 508^(b)) A1.88 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—O—(3-CH₃—Ph) 115-117^(a)) A1.89 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—S—(4-Cl—Ph) 139-141^(a)) A1.90 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—S—Ph 106-107^(a)) A1.91 (CH₃)₂N C₃H₇-i (S) —(CH₂)₂—N(C₂H₅)—Ph 521^(b)) A1.92 (CH₃)₂N C₃H₇-i (S) —CH(CH₃)—CH₂—O—(4-Cl—Ph) 542^(b)) A1.93 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(2-Cl—Ph) 161-162^(a) A1.94 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(2-naphthyl) 181-183^(a)) A1.95 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—O—(3-F—Ph) resin, 543^(c)) A1.96 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—S—(4-Cl—Ph) 575^(b)) A1.97 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—S—Ph resin, 541^(c)) A1.98 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —(CH₂)₂—N(C₂H₅)—Ph 554^(b)) A1.99 Cl—CH₂—CH₂—CH₂— C₃H₇-i (S) —CH(CH₃)—CH_(2—O—(4-Cl—Ph)) 105-107^(a)) A1.100 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(2-Cl—Ph) 123-124^(a)) A1.101 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(3-F—Ph) 124-126^(a)) A1.102 C₂H₅ C₄H₉-s (S) —(CH₂)₂—O—(4-CH₃—Ph) 136-137^(a)) A1.103 C₂H₅ C₄H₉-s (S) —(CH₂)₂—N(C₂H₅)—Ph 520^(b)) A1.104 C₂H₅ C₄H₉-s (S) —CH(CH₃)—CH₂—O—(4-Cl—Ph) resin, 539^(c)) A1.105 C₂H₅ C₃H₇-n (S) —CH₂—CH═CH—(4-Cl—Ph) 139-140^(a) A1.106 C₂H₅ C₄H₉-s (S) —CH₂—CH═CH—(4-Cl—Ph) 143-145^(a)) A1.107 C₂H₅ C₃H₅-c (S) —CH₂—CH═CH—(4-Cl—Ph) 135-136^(a)) A1.108 C₂H₅ CH₂—C═CH (R,S) —CH₂—CH═CH—(4-Cl—Ph) 142-143^(a)) A1.109 C₂H₅ C₂H₅ (S) —CH₂—CH═CH—(4-Cl—Ph) 125-127^(a)) A1.110 C₂H₅ CH(OH)—CH₃ (S) —CH₂—CH═CH—(4-Cl—Ph) 139-141^(a)) ^(a))m.p. (° C.), ^(b))mass spectra m/e (M⁺ + 1), ^(c))mass spectra m/e (M⁺ − 1), *⁾Configuration on the α-C-atom in the amino acid moiety Ph means phenyl

EXAMPLE A2.1. E-(S)-2-Ethanesulfonylamino-N-{2-[3-methoxy-4-(3-phenyl-allyloxy)-phenyl]-ethyl}-3-methyl-butyramide

A mixture of (S)-N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-2-methanesulfonylamino-3-methyl-butyramide (2.5 g), E-(3-bromo-propenyl)-benzene(1.5 g) and sodium methoxide (9 ml 1M solution in methanol) in methanol (30 ml) is heated to reflux for 4 hours. Upon cooling water (400 ml) is added. The mixture is extracted with ethyl acetate (2×300 ml). The organic layers are washed with brine (100 ml), dried (MgSO₄) and evaporated. The resulting residue is purified by recrystallisation (ethyl acetate/hexane). E-(S)-2-Ethanesulfonylamino-N-{2-[3-methoxy-4-(3-phenyl-allyloxy)-phenyl]-ethyl}-3-methyl-butyramide is obtained, m.p. 128-133° C.

Analogously to example A2.1 the compounds listed in table A2 are obtained.

TABLE A2

No. R₁ R₃ *⁾ A Data^(a), b)) A2.01 C₂H₅ C₃H₇-i (S) Ph 128-133^(a)) A2.02 CH₃ C₃H₇-i (S) Ph Oil, 510^(b)) A2.03 C₂H₅ C₃H₇-i (S) 4-Cl—Ph 147-149^(a)) A2.04 CH₃ C₃H₇-i (S) 4-Cl—Ph 144-149^(a)) A2.05 (CH₃)₂N C₃H₇-i (S) 4-Cl—Ph  79-82^(a)) A2.06 C₂H₅ C₃H₇-i (S) 3-CF₃—Ph resin, 541^(c)) A2.07 CH₃ C₃H₇-i (S) 3-CF₃—Ph 113-114^(a)) A2.08 (CH₃)₂N C₃H₇-i (S) 3-CF₃—Ph 105-107^(a)) A2.09 C₂H₅ C₃H₇-i (S) 2-F—Ph 146-148^(a)) A2.10 CH₃ C₃H₇-i (S) 2-F—Ph resin, 479^(b)) A2.11 (CH₃)₂N C₃H₇-i (S) 2-F—Ph 112-114^(a)) A2.12 C₂H₅ C₃H₇-i (S) 3,4-Cl₂—Ph 126-128^(a)) A2.13 CH₃ C₃H₇-i (S) 3,4-Cl₂—Ph 133-135^(a)) A2.14 C₂H₅ C₃H₇-i (S) 4-Br—Ph 153-155^(a)) A2.15 (CH₃)₂N C₃H₇-i (S) 4-Br—Ph  96-98^(a)) A2.16 CH₃ C₃H₇-i (S) 4-Br—Ph 159-162^(a)) A2.17 (CH₃)₂N C₃H₇-i (S) 3,4-Cl₂—Ph 129-131^(a)) A2.18 C₂H₅ C₃H₇-i (S) 1-naphthyl  99-102^(a)) A2.19 CH₃ C₃H₇-i (S) 1-naphthyl 123-125^(a)) ^(a))m.p. (° C.), ^(b))mass spectra m/e (M⁺ + 1), ^(c))mass spectra m/e (M⁺ − 1) *⁾Configuration on the α-C-atom in the amino acid moiety Ph means phenyl

In analogy to Example A2.1 the compounds of the following Table are obtained

No R₁ R₃ *) CR₉R₁₀R₁₁ Data A2.100 C₂H₅ C₃H₇-i (S) —(CH₂)₂—NH-Ph Oil ¹H-NMR (CDCl₃) δ (ppm): 0.89 (d, 3H); 0.95 (d, 3H); 1.32 (t, 3H); 1.9-2.15 (m, 1H); 2.75 (t, 2H); 2.98 (q, 2H); 3.25-3.35 (m, 2H); 3.45-3.6 (m, 3H); 3.8-3.9 (m, 5H); 5.20 (d, 1H); 6.09 (t, 1H); 6.65- 6.85 (m, 6H); 7.1-7.3 (m, 2H) A2.101 C₂H₅ C₃H₇-i (S) —(CH₂)₂—NH-Ph Oil ¹H-NMR (CDCl₃) δ (ppm): 0.89 (d, 3H); 0.99 (d, 3H); 1.8- 1.95 (m, 1H); 2.6- 2.8 (m, 2H); 2.96 (s, 3H); 3.02 (s, 3H); 3.15-3.35 (m, 4H); 3.8-3.9 (m, 5H); 3.96 (dd, 1H); 4.25 (t, 3H); 5.45 (d, 1H); 6.6-6.9 (m, 6H); 7.1-7.25 (m, 2H)

EXAMPLE A3.1 Z-(S)-2-Methanesulfonylamino-N-{2-[3-methoxy-4-(3-phenyl-allyloxy)-phenyl]-ethyl}-3-methyl-butyramide

A mixture of (S)-N-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-2-methanesulfonylamino-3-methyl-butyramide (3.5 g), toluene-4-sulfonic acid 3-phenyl-prop-2-ynyl ester (4.3 g) and sodium methoxide (20 ml 1M solution in methanol) in methanol (50 ml) is heated to reflux for 2 hours. Upon cooling brine (200 ml) is added. The mixture is extracted with ethyl acetate (2×200 ml). The organic layers are washed with brine (50 ml), dried (MgSO₄) and evaporated. The resulting residue, (S)-2-methanesulfonylamino-N-{2-[3-methoxy-4-(3-phenyl-prop-2-ynyloxy)-phenyl]-ethyl}-3-methyl-butyramide, is purified by recrystallisation (ethyl acetate/hexane).

This compound (1.7 g) is dissolved in tetrahyrofuran (40 ml), Lindlar-catalyst (5%-Pd on CaSO₄; 340 mg), 3,6-dithia-1,8-octandiol (4 mg) and 2,2′-(ethylenedithio)-diethanol (4 mg) are added. The resulting mixture is shaken under a hydrogen atmosphere at room temperature and at normal pressure for 24 h. It is then filtered and evaporated.

Z-(S)-2-Methanesulfonylamino-.N.-{2-[3-methoxy-4-(3-phenyl-allyloxy)-phenyl]-ethyl}-3-methyl-butyramide is obtained, oil.

Analogously to example A3.1 the compounds listed in table A3 are obtained.

TABLE A3

No. R₁ R₃ *⁾ A Data A3.01 CH₃ C₃H₇-i (S) Ph Oil, 461^(b)) A3.02 C₂H₅ C₃H₇-i (S) Ph Oil, 475^(b)) A3.03 C₂H₅ C₃H₇-i (S) 4-Cl—Ph 141-143^(a)) ^(a))m.p. (° C.), ^(b))mass spectra m/e (M⁺ + 1) *⁾Configuration on the α-C-atom in the amino acid moiety Ph means phenyl

EXAMPLE A3.2 Z-(S)-N-(2-{4-[3-(4-Chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-2-ethanesulfonylamino-3-methyl-butyramide

To a mixture of BOC-L-Valin (48 g), 4-(2-Amino-ethyl)-2-methbxy-phenol hydrochloride (45 g) and diethyl-isopropylamine (64.6 g) in dimethylformamide (900 ml) is added benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (97.8 g) in one portion. The reaction mixture is stirred for 4 hours at room temperature. Water (1000 ml) is then added. The mixture is extracted with ethyl acetate (2×500 ml). The organic layers organic layers are washed with brine (2×400 ml), dried (MgSO₄) and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2). (S)-{1-[2-(4-Hydroxy-3-methoxy-phenyl)-ethylcarbamoyl]-2-methyl-propyl}-carbamic acid tert.-butyl ester is obtained.

A mixture of (S)-{1-[2-(4-hydroxy-3-methoxy-phenyl)-ethylcarbamoyl]-2-methyl-propyl}-carbamic acid -tert.-butyl ester (36.6 g) toluene-4-sulfonic acid 3-(4-chloro-phenyl)-prop-2-ynyl ester (50 g), sodium iodide (20 mg) and sodium methoxide (200 ml 1M solution in methanol) in methanol (300 ml) is heated to reflux for 2 hours. Upon cooling brine (1500 ml) is added. the mixture is extracted with ethyl acetate (2×700 ml). The organic layers are washed with brine (200 ml), dried (MgSO₄) and evaporated. The resulting residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2) and recrystallised (ethyl acetate/hexane). (S)-[1-(2-{4-[3-(4-Chloro-phenyl)-prop-2-ynyloxy]-3-methoxy-phenyl}-ethylcarbamoyl)-2-methyl-propyl]-carbamic acid-tert.-butyl ester is obtained.

To (S)-[1-(2-{4-[3-(4-chloro-phenyl)-prop-2-ynyloxy]-3-methoxy-phenyl}ethylcarbamoyl)-2-methyl-propyl]-carbamic acid-tert.-butyl ester (18 g) in tetrahyrofuran (180 ml), Lindlar-catalyst (5%-Pd on CaSO₄; 7.2 g), 3,6-dithia-1,8-octandiol (45 mg) and 2,2′-(ethylenedithio)-diethanol (45 mg) are added. The resulting mixture is shaken under a hydrogen atmosphere at room temperature and at normal pressure for 5 hours. It is then filtered and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:2) and recrystallised (ethyl acetate/hexane). Z-(S)-[1-(2-{4-[3-(4-Chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethylcarbamoyl)-2-methyl-propyl]-carbamic acid-tert.-butyl ester is obtained, m.p. 82-84° C.

To concentrated hydrochloric acid (2.7 g; precooled to 0° C.) is added. Z-(S)-[1-(2-{4-[3-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethylcarbamoyl)-2-methyl-propyl]-carbamic acid -tert.-butyl ester (3 g) in dichloromethane (20 ml). The resulting mixture is vigorously stirred for 16 hours at room temperature. The mixture is adjusted to pH 12 by adding 2N sodium hydroxide. It is then extracted with dichloromethane (2×100 ml). The organic layers are washed with brine (100 ml), dried (K₂CO₃) and evaporated. Z-(S)-2-Amino-.N.-(2-{4-[3-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide is obtained.

To Z-(S)-2-amino-N-(2-{4-[3-(4-chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-3-methyl-butyramide (1.7 g), and triethylamine (1 g) in dioxane (30 ml) is added ethane sulfochloride (0.52 g). The mixture is stirred at room temperature for 16 hours. Brine (200 ml) is added. It is extracted with ethyl acetate (2×200 ml). The organic layers are washed with brine (100 ml) dried and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:1) and recrystallised. Z-(S)-N-(2-{4-[3-(4-Chloro-phenyl)-allyloxy]-3-methoxy-phenyl}-ethyl)-2-ethanesulfonylamino-3-methyl-butyramide is obtained, m.p. 141-143° C.

EXAMPLE B1.1 {4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile

A mixture of 4-hydroxy-3-methoxy-benzyl alcohol (14.7 g) and sodium cyanide (5 g) in dimethylformamide (200 ml) is stirred under an atmosphere of nitrogen for 3 hours at +120° C. The mixture is then cooled to +100° C. and 1-(2-bromo-ethoxy)-4-fluoro-benzene (25 g) is added in one portion. The mixture is stirred at +100° C. for another 4 hours. Upon cooling water (800 ml) is added. The mixture is extracted with ethyl acetate (2×500 ml). The organic phases are washed with brine (2×500 ml), dried (MgSO₄) and evaporated. The residue is recrystallised from ethyl acetate/hexane. {4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile is obtained, m.p. 126-128° C.

Analogously to example B1.1 the compounds listed in table B1 are obtained.

Ph means phenyl

TABLE B1

No CR₉R₁₀R₁₁ Data B1.01 —(CH₂)₂—O—(4-F—Ph) 126-128^(a)) B1.02 —(CH₂)₂—O—Ph 108-109^(a)) B1.03 —(CH₂)₂—O—(4-Cl—Ph) 137-139^(a) B1.04 —(CH₂)₂—O—(2-Cl—Ph)  93-95^(a)) B1.05 —(CH₂)₂—O—(2-naphthyl) 106-111^(a)) B1.06 —(CH₂)₂—O—(3-F—Ph)  90-92^(a)) B1.07 —(CH₂)₂—O—(4-CH₃—Ph) 100-102^(a)) B1.08 —(CH₂)₂—O—(3-CH₃—Ph) 104-106^(a)) B1.09 —(CH₂)₂—O—(3,4-Cl₂—Ph) 107-110^(a)) B1.10 —(CH₂)₂—O—(4-Br—Ph) 136-141^(a)) B1.11 —(CH₂)₂—O—(2-Br—Ph)  99-108^(a)) B1.12 —CH(CH₃)—CH₂—O—(4-Cl—Ph) Oil, ¹H-NMR (CDCl₃) δ (ppm): 1.45(d, 3H); 3.70(s, 2H); 3.84(s, 3H); 3.95-4.2(m, 2H); 4.6-4.7(m, 1H); 6.8-7.0 (m, 5H); 7.2-7.25(m, 2H) B1.13 —(CH₂)₂—S—Ph Oil, ¹H-NMR (CDCl₃) δ (ppm): 3.32(t, 2H); 3.67(s, 2H); 3.86(s,3H); 4.17(t, 2H); 6.7-6.8(m, 3H); 7.15-7.45(m, 5H) B1.14 —(CH₂)₂—S—(4-Cl—Ph) 91-93^(a)) B1.15 —(CH₂)₂—N(CH₃)—Ph Oil, 297^(b)) B1.16 —(CH₂)₂—N(C₂H₅)—Ph Oil, ¹H-NMR (CDCl₃) δ (ppm): 1.19(t, 3H); 3.46(q, 2H); 3.68(s, 2H); 3.77(t, 2H); 3.88(s, 3H); 4.14(t, 2H); 6.6-6.85(m, 6H); 7.2-7.3(m, 2H) ^(a))m.p. (° C.), ^(b))mass spectra m/e (M⁺ + 1)

EXAMPLE B2.1 2-{4-[2-(4-Fluoro-phenoxy]-ethoxyl-3-methoxy-phenyl}-ethylamine

A mixture of {4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-acetonitrile (14.8 g), liquid ammonia (8.4 g) and Raney-nickel (4.5 g) in tetrahydrofuran (120 ml) is shaken in an autoclave under hydrogen (130 bar) at +60° C. for 2 hours. The reaction mixture is filtered and evaporated. 2-{4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine is obtained as an oil.

Analogously to example B2.1 the compounds listed in table B2 are obtained.

TABLE B2

No CR₉R₁₀R₁₁ Data B2.01 —(CH₂)₂—O—(4-F—Ph) oil, ¹H-NMR(CDCl₃) δ (ppm): 1.60(s, 2H); 2.75(t, 2H); 3.00(t, 2H); 3.85(s, 3H); 4.25-4.35(m, 4H); 6.7-7.1 (m, 7H) B2.02 —(CH₂)₂—O—Ph oil, ¹H-NMR(CDCl₃) δ (ppm): 1.59(s, 2H); 2.73(t, 2H); 3.00(t, 2H); 3.85(s, 3H); 4.3-4.35(m, 4H); 6.7-6.75(m, 2H); 6.85-7.0(m, 4H); 7.2-7.35(m, 2H) B2.03 —(CH₂)₂—O—(4-Cl—Ph) oil, ¹H-NMR(CDCl₃) δ (ppm): 1.50(s, 2H); 2.69 (t, 2H); 2.94(t, 2H); 3.84(s, 3H); 4.3-4.35(m, 4H); 6.7-6.9(m, 5H); 7.15-7.3 (m, 2H) B2.04 —(CH₂)₂—O—(2-Cl—Ph) 69-71^(a)) B2.05 —(CH₂)₂—O—(2-naphthyl) oil, 338^(b)) B2.06 —(CH₂)₂—O—(3-F—Ph) oil, 306^(b)) B2.07 —(CH₂)₂—O—(4-CH₃—Ph) resin, ¹H-NMR(CDCl₃) δ (ppm): 1.31(s, 2H); 2.28 (s, 3H); 2.69(t, 2H); 2.95(t, 2H); 3.85(s, 3H); 4.25- 4.4(m, 4H); 6.7-6.95(m, 5H); 7.05-7.1(m, 2H) B2.08 —(CH₂)₂—O—(3-CH₃—Ph) resin, 302^(b)) B2.09 —(CH₂)₂—O—(3,4-Cl₂—Ph) resin, ¹H-NMR(CDCl₃) δ (ppm): 1.22(s, 2H); 2.69 (t, 2H); 2.95(t, 2H); 3.84(s, 3H); 4.2-4.4(m, 4H); 6.7-7.3(m, 6H); B2.10 —(CH₂)₂—O—(4-Br—Ph) resin, 366^(b)) B2.11 —(CH₂)₂—O—(2-Br—Ph) oil, 366^(b)) B2.12 —CH(CH₃)—CH₂—O—(4- oil, 336^(b)) Cl—Ph) B2.13 —(CH₂)₂—S—Ph oil, 304^(b)) B2.14 —(CH₂)₂—S—(4-Cl—Ph) 338^(b)) B2.15 —(CH₂)₂—N(CH₃)—Ph oil, 301 ^(b)) B2.16 —(CH₂)₂—N(C₂H₅)—Ph oil, 315^(b)) ^(a))m.p.(° C.), ^(b)) mass spectra m/e (M⁺ + 1), Ph means phenyl

To 2-{4-[2-(4-fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine (15.7 g) dissolved in diethylether (200 ml) is added 1M hydrogen chloride solution in diethylether (75 ml). The resulting residue is isolated by separation in a centrifuge and decantation. 2-{4-[2-(4-Fluoro-phenoxy)-ethoxy]-3-methoxy-phenyl}-ethylamine hydrochloride is obtained.

EXAMPLE C1.1 [3-Methoxy-4-(3-phenyl-prop-2-ynyloxy)-phenyl]-acetonitrile

A mixture of (4-hydroxy-3-methoxy-phenyl)-acetonitrile (17.4 g) and sodium cyanide (6.6 g) in dimethylformamide (250 ml) is stirred under an atmosphere of nitrogen for 3 hours at +120° C. The mixture is then cooled to +60° C. and toluene-4-sulfonic acid 3-phenyl-prop-2-ynyl ester (39 g) in dimethylformamid (50 ml)is added during 5 minutes. It is stirred at +65° C. for another 4 hours. Upon cooling water (800 ml) is added. The mixture is extracted with ethyl acetate (2×500 ml). The organic phases are washed with brine (2×500 ml), dried (MgSO₄) and evaporated. The residue is purified by flash column chromatography on silica gel (ethyl acetate/hexane 1:3) and recrystallised from ethyl acetate/hexane. [3-Methoxy-4-(3-phenyl-prop-2-ynyloxy)-phenyl]-acetonitrile is obtained, m.p. 74-75° C.

Analogously to example C1.1 the compounds listed in table C1 are obtained.

Ph means phenyl

TABLE C1

No A m.p. (° C.) C1.01 Ph 74-75 C1.02 4-Cl—Ph 108—109 C1.03 4-F—Ph oil

Analogously to the above Examples the following compounds of Tables 1 to 37 may be prepared. In the tables Ph means phenyl.

Table 1: Compounds represented by the Formula I.1 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 2: Compounds represented by the Formula I.2 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 3: Compounds represented by the Formula I.3 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 4: Compounds represented by the Formula I.4 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 5: Compounds represented by the Formula I.5 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 6: Compounds represented by the Formula I.6 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 7: Compounds represented by the Formula I.7 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 8: Compounds represented by the Formula I.8 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 9: Compounds represented by the Formula I.9 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 10: Compounds represented by the Formula I.10 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 11: Compounds represented by the Formula I.11 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 12: Compounds represented by the Formula I.12 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 13: Compounds represented by the Formula I.13 wherein the combination of the groups R₁, R₃, R₉, R₁₀ and R₁₁ corresponds to each row in table A.

Table 14: Compounds represented by the Formula I.14 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 15: Compounds represented by the Formula I.15 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 16: Compounds represented by the Formula I.16 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 17: Compounds represented by the Formula I.17 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 18: Compounds represented by the Formula I.18 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 19: Compounds represented by the Formula I.19 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 20: Compounds represented by the Formula I.20 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 21: Compounds represented by the Formula I.21 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 22: Compounds represented by the Formula I.22 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 23: Compounds represented by the Formula I.23 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 24: Compounds represented by the Formula I.24 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 25: Compounds represented by the Formula I.25 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 26: Compounds represented by the Formula I.26 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 27: Compounds represented by the Formula I.27 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 28: Compounds represented by the Formula I.28 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 29: Compounds represented by the Formula I.29 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 30: Compounds represented by the Formula I.30 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 31: Compounds represented by the Formula I.31 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 32: Compounds represented by the Formula I.32 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 33: Compounds represented by the Formula I.33 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 34: Compounds represented by the Formula I.34 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 35: Compounds represented by the Formula I.35 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 36: Compounds represented by the Formula I.36 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

Table 37: Compounds represented by the Formula I.37 wherein the combination of the groups R₉, R₁₀ and R₁₁ corresponds to each row in table B.

TABLE A No. R₁ R₃ CR₉R₁₀R₁₁ 001 CH₃ C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 002 C₂H₅ C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 003 (CH₃)₂N— C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 004 C₃H₇-i C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 005 C₃H₇-n C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 006 ClH₂C—CH₂—CH₂— C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 007 H₂C═CH— C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 008 CH₃—SO₂—CH₂— C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 009 CF₃ C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 010

C₃H₇-i CH₂—CH₂—O—(4-F—Ph) 011 CH₃ C₂H₅ CH₂—CH₂—O—(4-F—Ph) 012 C₂H₅ C₂H₅ CH₂—CH₂—O—(4-F—Ph) 013 (CH₃)₂N— C₂H₅ CH₂—CH₂—O—(4-F—Ph) 014 C₃H₇-i C₂H₅ CH₂—CH₂—O—(4-F—Ph) 015 C₃H₇-n C₂H₅ CH₂—CH₂—O—(4-F—Ph) 016 ClH₂C—CH₂—CH₂— C₂H₅ CH₂—CH₂—O—(4-F—Ph) 017 H₂C═CH— C₂H₅ CH₂—CH₂—O—(4-F—Ph) 018 CH₃—SO₂—CH₂— C₂H₅ CH₂—CH₂—O—(4-F—Ph) 019 CF₃ C₂H₅ CH₂—CH₂—O—(4-F—Ph) 020

C₂H₅ CH₂—CH₂—O—(4-F—Ph) 021 CH₃ C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 022 C₂H₅ C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 023 (CH₃)₂N— C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 024 C₃H₇-i C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 025 C₃H₇-n C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 026 ClH₂C—CH₂—CH₂— C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 027 H₂C═CH— C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 028 CH₃—SO₂—CH₂— C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 029 CF₃ C₃H₇-n CH₂—CH₂—O—(4-F—Ph) 030

C₃H₇-s CH₂—CH₂—O—(4-F—Ph) 031 CH₃ C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 032 C₂H₅ C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 033 (CH₃)₂N— C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 034 C₃H₇-i C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 035 C₃H₇-n C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 036 ClH₂C—CH₂—CH₂— C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 037 H₂C═CH— C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 038 CH₃—SO₂—CH₂— C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 039 CF₃ C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 040

C₃H₉-s CH₂—CH₂—O—(4-F—Ph) 041 CH₃ C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 042 C₂H₅ C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 043 (CH₃)₂N— C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 044 C₃H₇-i C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 045 C₃H₇-n C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 046 ClH₂C—CH₂—CH₂— C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 047 H₂C═CH— C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 048 CH₃—SO₂—CH₂— C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 049 CF₃ C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 050

C₃H₅-cycl CH₂—CH₂—O—(4-F—Ph) 051 CH₃ CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 052 C₂H₅ CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 053 (CH₃)₂N— CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 054 C₃H₇-i CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 055 C₃H₇-n CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 056 ClH₂C—CH₂—CH₂— CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 057 H₂C═CH— CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 058 CH₃—SO₂—CH₂— CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 059 CF₃ CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 060

CH₂—CH═CH₂ CH₂—CH₂—O—(4-F—Ph) 061 CH₃ CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 062 C₂H₅ CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 063 (CH₃)₂N— CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 064 C₃H₇-i CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 65 C₃H₇-n CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 066 ClH₂C—CH₂—CH₂— CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 067 H₂C═CH— CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 068 CH₃—SO₂—CH₂— CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 069 CF₃ CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 070

CH₂—C≡CH CH₂—CH₂—O—(4-F—Ph) 071 CH₃ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 072 C₂H₅ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 073 (CH₃)₂N— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 074 C₃H₇-i C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 075 C₃H₇-n C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 076 ClH₂C—CH₂—CH₂— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 077 H₂C═CH— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 078 CH₃—SO₂—CH₂— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 079 CF₃ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 080

C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-F—Ph) 081 CH₃ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 082 C₂H₅ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 083 (CH₃)₂N— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 084 C₃H₇-i H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 085 C₃H₇-n H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 086 ClH₂C—CH₂—CH₂— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 087 H₂C═CH— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 088 CH₃—SO₂—CH₂— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 089 CF₃ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 090

H₃C—CH₂(OH)— CH₂—CH₂—O—(4-F—Ph) 091 CH₃ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 092 C₂H₅ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 093 (CH₃)₂N— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 094 C₃H₇-i H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 095 C₃H₇-n H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 096 ClH₂C—CH₂—CH₂— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 097 H₂C═CH— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 098 CH₃—SO₂CH₂— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 099 CF₃ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 100

H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-F—Ph) 101 CH₃ HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 102 C₂H₅ HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 103 (CH₃)₂N— HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 104 C₃H₇-i HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 105 C₃H₇-n HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 106 ClH₂C—CH₂—CH₂— HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 107 H₂C═CH— HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 108 CH₃—SO₂CH₂— HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 109 CF₃ HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 110

HS—CH₂ CH₂—CH₂—O—(4-F—Ph) 111 CH₃ C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 112 C₂H₅ C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 113 (CH₃)₂N— C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 114 C₃H₇-i C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 115 C₃H₇-n C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 116 ClH₂C—CH₂—CH₂— C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 117 H₂C═CH— C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 118 CH₃—SO₂—CH₂— C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 119 CF₃ C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 120

C₃H₇-i CH₂—CH₂—O—(4-Cl—Ph) 121 CH₃ C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 122 C₂H₅ C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 123 (CH₃)₂N— C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 124 C₃H₇-i C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 125 C₃H₇-n C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 126 ClH₂C—CH₂—CH₂— C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 127 H₂C═CH— C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 128 CH₃—SO₂—CH₂— C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 129 CF₃ C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 130

C₂H₅ CH₂—CH₂—O—(4-Cl—Ph) 131 CH₃ C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 132 C₂H₅ C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 133 (CH₃)₂N— C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 134 C₃H₇-i C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 135 C₃H₇-n C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 136 ClH₂C—CH₂—CH₂— C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 137 H₂C═CH— C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 138 CH₃—SO₂—CH₂— C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 139 CF₃ C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 140

C₃H₇-n CH₂—CH₂—O—(4-Cl—Ph) 141 CH₃ C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 142 C₂H₅ C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 143 (CH₃)₂N— C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 144 C₃H₇-i C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 145 C₃H₇-n C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 146 ClH₂C—CH₂—CH₂— C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 147 H₂C═CH— C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 148 CH₃—SO₂—CH₂— C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 149 CF₃ C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 150

C₄H₉-s CH₂—CH₂—O—(4-Cl—Ph) 151 CH₃ C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 152 C₂H₅ C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 153 (CH₃)₂N— C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 154 C₃H₇-i C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 155 C₃H₇-n C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 156 ClH₂C—CH₂—CH₂— C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 157 H₂C═CH— C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 158 CH₃—SO₂—CH₂— C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 159 CF₃ C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 160

C₃H₅-cycl CH₂—CH₂—O—(4-Cl—Ph) 161 CH₃ CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 162 C₂H₅ CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 163 (CH₃)₂N— CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 164 C₃H₇-i CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 165 C₃H₇-n CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 166 ClH₂C—CH₂—CH₂— CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 167 H₂C═CH— CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 168 CH₃—SO₂CH₂— CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 169 CF₃ CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 170

CH₂—CH═CH₂ CH₂—CH₂—O—(4-Cl—Ph) 171 CH₃ CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 172 C₂H₅ CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 173 (CH₃)₂N— CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 174 C₃H₇-i CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 175 C₃H₇-n CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 176 ClH₂C—CH₂—CH₂— CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 177 H₂C═CH— CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 178 CH₃—SO₂—CH₂— CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 179 CF₃ CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 180

CH₂—C≡CH CH₂—CH₂—O—(4-Cl—Ph) 181 CH₃ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 182 C₂H₅ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 183 (CH₃)₂N— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 184 C₃H₇-i C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 185 C₃H₇-n C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 186 ClH₂C—CH₂—CH₂— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 187 H₂C═CH— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 188 CH₃—SO₂—CH₂— C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 189 CF₃ C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 190

C₃H₅-cycl—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 191 CH₃ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 192 C₂H₅ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 193 (CH₃)₂N— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 194 C₃H₇-i H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 195 C₃H₇-n H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 196 ClH₂C—CH₂—CH₂— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 197 H₂C═CH— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 198 CH₃—SO₂—CH₂— H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 199 CF₃ H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 200

H₃C—CH₂(OH)— CH₂—CH₂—O—(4-Cl—Ph) 201 CH₃ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 202 C₂H₅ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 203 (CH₃)₂N— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 204 C₃H₇-i H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 205 C₃H₇-n H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 206 ClH₂C—CH₂—CH₂— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 207 H₂C═CH— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 208 CH₃—SO₂—CH₂— H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 209 CF₃ H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 210

H₃C—S—CH₂—CH₂— CH₂—CH₂—O—(4-Cl—Ph) 211 CH₃ HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 212 C₂H₅ HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 213 (CH₃)₂N— HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 214 C₃H₇-i HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 215 C₃H₇-n HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 216 ClH₂C—CH₂—CH₂— HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 217 H₂C═CH— HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 218 CH₃—SO₂—CH₂— HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 219 CF₃ HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph) 220

HS—CH₂ CH₂—CH₂—O—(4-Cl—Ph)

TABLE B No. CR₉R₁₀R₁₁ 001 CH₂—CH═CH—Ph 002 CH₂—CH═CH—(4-F—Ph) 003 CH₂—CH═CH—(4-Cl—Ph) 004 CH₂—CH═CH—(4-Br—Ph) 005 CH₂—CH═CH—(4-CH₃—Ph) 006 CH₂—CH═CH—(4-OCH₃—Ph) 007 CH₂—CH═CH—(4-NO₂—Ph) 008 CH₂—CH═CH—(4-CF₃—Ph) 009 CH₂—CH═CH—(4-CN—Ph) 010 CH₂—CH═CH—(3-Br—Ph) 011 CH₂—CH═CH—(3-Cl—Ph) 012 CH₂—CH═CH—(3-Cl—Ph) 013 CH₂—CH═CH—(3-CH₃—Ph) 014 CH₂—CH═CH—(2-Cl—Ph) 015 CH₂—CH═CH—(2-F—Ph) 016 CH₂—CH═CH—(2,4-Cl₂—Ph) 017 CH₂—CH═CH—(3-Cl—4-CH₃—Ph) 018 CH₂—CH═CH—(3-Cl—4-F—Ph) 019 CH₂—CH═CH—(3-F—4-Cl—Ph) 020 CH₂—CH═CH—(3,4-Cl₂—Ph) 021 CH₂—CH═CH—(3,4-F₂—Ph) 022 CH₂—CH═CH—(2,5-Cl₂—Ph) 023 CH₂—CH═CH—(3,5-Cl₂—Ph) 024 CH₂—CH═CH—2,4,5-Cl₃—Ph) 025

026

027

028

029

030

031

032

033

034 CH(CH₃)—CH═CH—Ph 035 CH(CH₃)—CH═CH—(4-F—Ph) 036 CH(CH₃)—CH═CH—(4-Cl—Ph) 037 CH(CH₃)—CH═CH—(4-Br—Ph) 038 C(CH₃)₂—CH═CH—Ph 039 C(CH₃)₂—CH═CH—(4-F—Ph) 040 C(CH₃)₂—CH═CH—(4-Cl—Ph) 041 CH₂—C(CH₃)═CH—Ph 042 CH₂—C(CH₃)═CH—(4-F—Ph) 043 CH₂—C(CH₃)═CH—(4-F—Ph) 044 CH₂—C(CH₃)═C(CH₃)—Ph 045 CH₂—C(CH₃)═C(CH₃)—(4-F—Ph) 046 CH₂—C(CH₃)═C(CH₃)—(4-Cl—Ph) 047 CH₂—CH═C(CH₃)—Ph 048 CH₂—CH═C(CH₃)—(4-F—Ph) 049 CH₂—CH═C(CH₃)—(4-Cl—Ph) 050 CH₂—CH₂—O—Ph 051 CH₂—CH₂—O—(4-Br—Ph) 052 CH₂—CH₂—O—(4-I—Ph) 053 CH₂—CH₂—O—(4-CH₃—Ph) 054 CH₂—CH₂—O—[4-(C₃H₇-i)—Ph] 055 CH₂—CH₂—O—(4-CF₃—Ph) 056 CH₂—CH₂—O—(4-OCH₃—Ph) 057 CH₂—CH₂—O—(4-OCF₃—Ph) 058 CH₂—CH₂—O—(4-SCF₃—Ph) 059 CH₂—CH₂—O—(4-SCH₃—Ph) 060 CH₂—CH₂—O—(4-CN—Ph) 061 CH₂—CH₂—O—(4-NO₂—Ph) 062 CH₂—CH₂—O—(4-CH₃OOC—Ph) 063 CH₂—CH₂—O—[4-(CH₂═CH)—Ph] 064 CH₂—CH₂—O—[4-(CH≡ C)—Ph] 065 CH₂—CH₂—O—[4-(CH₂—Ph)—Ph] 066 CH₂—CH₂—O—[4-(C₆H₁₁-cycl)—Ph] 067 CH₂—CH₂—O—[4-(CH₃—SO₂)—Ph] 068 CH₂—CH₂—O—(4-CHO—Ph) 069 CH₂—CH₂—O—[4-(CH₃—CO)—Ph] 070 CH₂—CH₂—O—(4-OH—Ph) 071 CH₂—CH₂—O—(4-NH₂—Ph) 072 CH₂—CH₂—O—[4-(CH₃)₂N—Ph] 073 CH₂—CH₂—O—[4-(CH₂═CH—CH₂)OOC—Ph] 074 CH₂—CH₂—O—(3-F—Ph) 075 CH₂—CH₂—O—(3-Cl—Ph) 076 CH₂—CH₂—O—(3-Br—Ph) 077 CH₂—CH₂—O—(3-OCHF₂—Ph) 078 CH₂—CH₂—O—(3-CH₃—Ph) 079 CH₂—CH₂—O—(3-CF₃—Ph) 080 CH₂—CH₂—O—(2-F—Ph) 081 CH₂—CH₂—O—(2-Cl—Ph) 082 CH₂—CH₂—O—(3,4-Cl₂—Ph) 083 CH₂—CH₂—O—[3,4-(CH₃)₂—Ph] 084 CH₂—CH₂—O—(3,4-F₂—Ph) 085 CH₂—CH₂—O—(3-Cl—4-F—Ph) 086 CH₂—CH₂—O—(3-F—4-Cl—Ph) 087 CH₂—CH₂—O—(3-CH₃—4-Cl—Ph) 088 CH₂—CH₂—O—(2,5-Cl₂—Ph) 089 CH₂—CH₂—O—(2,6-Cl₂—Ph) 090 CH₂—CH₂—O—(2,4-Cl₂—Ph) 091 CH₂—CH₂—O—(2,4-F₂—Ph) 092 CH₂—CH₂—O—(3,5-F₂—Ph) 093 CH₂—CH₂—O—(3,5-Cl₂—Ph) 094 CH₂—CH₂—O—(2,4,5-Cl₃—Ph) 095 CH₂—CH₂—O—(2,3,4,5,6-F₅—Ph) 096

097

098

099

100

101

102

103

104

105

106 CH(CH₃)—CH₂—O—Ph 107 CH(CH₃)—CH₂—O—(4-F—Ph) 108 CH(CH₃)—CH₂—O—(4-Cl—Ph) 109 CH(C₂H₅)—CH₂—O—(4-F—Ph) 110 CH(C₂H₅)—CH₂—O—(4-Cl—Ph) 111 C(CH₃)₂—CH₂—O—(4-F—Ph) 112 C(CH₃)₂—CH₂—O—(4-Cl—Ph) 113 CH₂—CH(CH₃)—O—Ph 114 CH₂—CH(CH₃)—O—(4-F—Ph) 115 CH₂—CH(CH₃)—O—(4-Cl—Ph) 116 CH₂—CH₂—S—Ph 117 CH₂—CH₂—S—(4-F—Ph) 118 CH₂—CH₂—S—(4-Cl—Ph) 119 CH₂—CH₂—S—(4-Br—Ph) 120 CH₂—CH₂—S—(3-F—Ph) 121 CH₂—CH₂—S—(3-Cl—Ph) 122 CH₂—CH₂—S—(3-Br—Ph) 123 CH₂—CH₂—S—(3,4-F₂—Ph) 124 CH₂—CH₂—S—(3,4-Cl₂—Ph) 125 CH₂—CH₂—NH—Ph 126 CH₂—CH₂—NH—(4-F—Ph) 127 CH₂—CH₂—NH—(4-Cl—Ph) 128 CH₂—CH₂—NH—(4-Br—Ph) 129 CH₂—CH₂—NH—(3-F—Ph) 130 CH₂—CH₂—NH—(3-Cl—Ph) 131 CH₂—CH₂—NH—(3-Br—Ph) 132 CH₂—CH₂—NH—(3,4-F₂—Ph) 133 CH₂—CH₂—NH—(3,4-Cl₂—Ph) 134 CH₂—CH₂—N(CH₃)—Ph 135 CH₂—CH₂—N(CH₃)—(4-F—Ph) 136 CH₂—CH₂—N(CH₃)—(4-Cl—Ph) 137 CH₂—CH₂—N(CH₃)—(4-Br—Ph) 138 CH₂—CH₂—N(CH₃)—(3-F—Ph) 139 CH₂—CH₂—N(CH₃)—(3-Cl—Ph) 140 CH₂—CH₂—N(CH₃)—(3-Br—Ph) 141 CH₂—CH₂—N(CH₃)—(3,4-F₂—Ph) 142 CH₂—CH₂—N(CH₃)—(3,4-Cl₂—Ph)

Formulations may be prepared analogously to those described in, for example, WO 95/30651.

Biological Examples

D-1: Action against Plasmopara Viticola on Vines

a) Residual-protective Action

Vine seedlings are sprayed at the 4- to 5-leaf stage with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 24 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation for 6 days at 95-100% relative humidity and 20° C.

b) Residual-curative Action

Vine seedlings are infected at the 4- to 5-leaf stage with a sporangia suspension of the fungus. After incubation for 24 hours in a humidity chamber at 95-100% relative humidity and 20° C., the infected plants are dried and sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After the spray coating has dried, the treated plants are placed in the humidity chamber again. Fungus infestation is evaluated 6 days after infection.

Compounds of Tables 1 to 37 exhibit a good fungicidal action against Plasmopara viticola on vines. Compounds A1.02, A1.03, A1.04, A1.03, A1.o5, A1.06, A1.07, A1.09, A1.10, A1.13, A1.14, A1.15, A1.16, A1.21, A1.23. A1.24, A1.25, A1.75, A1.76, A1.78, A1.80, A.107, A1.108, A2.03, A2.04, A2.09, A2.10, A2.16, A3.02 and A3.03 completely inhibit fungal infestation in this test.

D-2: Action against Phylophthora on Tomato Plants

a) Residual-protective Action

After a cultivation period of 3 weeks, tomato plants are sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 5 days at 90-100% relative humidity and 20° C.

b) Systemic Action

After a cultivation period of 3 weeks, tomato plants are watered with a spray mixture (0.02% active ingredient based on the volume of the soil) prepared from a wettable powder formulation of the test compound. Care is taken that the spray mixture does not come into contact with the parts of the plants that are above the ground. After 96 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C. Compounds of Tables 1 to 37 exhibit a long-lasting effect against fungus infestation. Compounds A1.02, A1.03, A1.04, A1.03, A1.o5, A1.06, A1.07, A1.09, A1.10, A1.13, A1.14, A1.15, A1.16, A1.21, A1.23. A1.24, A1.25, A1.75, A1.76, A1.78, A1.80, A.107, A1.108, A2.03, A2.04, A2.09, A2.10, A2.16, A3.02 and A3.03 completely inhibit fungal infestation in this test.

D-3: Action against Phytophthora on Potato Plants

a) Residual-protective Action

2-3 week old potato plants (Bintje variety) are sprayed with a spray mixture (0.02% active ingredient) prepared from a wettable powder formulation of the test compound. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C.

b) Systemic Action

2-3 week old potato plants (Bintje variety) are watered with a spray mixture (0.02% active ingredient based on the volume of the soil) prepared from a wettable powder formulation of the test compound. Care is taken that the spray mixture does not come into contact with the parts of the plants that are above the ground. After 48 hours, the treated plants are infected with a sporangia suspension of the fungus. Fungus infestation is evaluated after incubation of the infected plants for 4 days at 90-100% relative humidity and 20° C. Fungal infestation is effectively controlled with compounds of Tables 1 to 37.

Compounds A1.02, A1.03, A1.04, A1.03, A1.o5, A1.06, A1.07, A1.09, A1.10, A1.13, A1.14, A1.15, A1.16, A1.21, A1.23. A1.24, A1.25, A1.75, A1.76, A1.78, A1.80, A.107, A1.108, A2.03, A2.04, A2.09, A2.10, A2.16, A3.02 and A3.03 completely inhibit fungal infestation in this test. 

What is claimed is:
 1. α-Sulfin- and α-sulfonamino acid amides of formula I

including the optical isomers thereof and mixtures of such isomers, wherein n is a number zero or one; R₁ is C₁-C₁₂alkyl, C₁-C₁₂alkyl substituted with C₁-C₄alkoxy, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, C₃-C₈cycloalkyl, cyano, C₁-C₆alkoxycarbonyl, C₃-C₆alkenyloxycarbonyl or C₃-C₆alkynyloxycarbonyl; C₃-C₈cycloalkyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl, or together are tetra- or penta-methylene; R₂ and R₃ are each independently hydrogen; C₁-C₈alkyl; C₁-C₈alkyl substituted with hydroxy, mercapto, C₁-C₄alkoxy or C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl; or the two groups R₂ and R₃ together with the carbon atom to which they are bonded form a three- to eight-membered hydrocarbon ring; R₄, R₅, R₆ and R₇ are each independently hydrogen or C₁-C₄alkyl; R₈ is C₁-C₆alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl; R₉ and R₁₀ are each independently hydrogen or C₁-C₄alkyl; and R₁₁ is either

 in wherein R₁₄, R₁₅, R₁₆ and R₁₇ are each independently hydrogen or C₁-C₄alkyl, X is oxygen, sulfur or —NR₁₈—, wherein R₁₈ is hydrogen or C₁-C₄alkyl, and A is optionally substituted mono- or polycylic aryl or heteroaryl.
 2. A compound according to claim 1 wherein R₁ is C₁-C₁₂alkyl, C₁-C₁₂alkyl substituted with C₁-C₄alkoxy, C₁-C₄alkylthio, or C₁-C₄alkylsulfonyl; C₂-C₁₂alkenyl; C₂-C₁₂alkynyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl, or together are tetra- or penta-methylene; and R₂ is hydrogen and R₃ is C₁-C₈alkyl; C₁-C₈alkyl substituted with hydroxy, mercapto, C₁-C₄alkoxy or C₁-C₄alkylthio; C₃-C₈alkenyl; C₃-C₈alkynyl; C₃-C₈cycloalkyl; C₃-C₈cycloalkyl-C₁-C₄alkyl; and R₄ is hydrogen or C₁-C₄alkyl and R₅, R₆ and R₇ are each hydrogen.
 3. A compound of formula I according to claim 1 wherein n is one; and R₁ is C₁-C₁₂alkyl, C₂-C₁₂alkenyl; C₁-C₁₂haloalkyl; or a group NR₁₂R₁₃ wherein R₁₂ and R₁₃ are each independently of the other hydrogen or C₁-C₆-alkyl; and R₂ is hydrogen and R₃ is C₁-C₄alkyl; C₃-C₄alkenyl or cyclopropyl; and R₄ is hydrogen, methyl or ethyl and R₅, R₆ and R₇ are each hydrogen; and R₈ is C₁-C₆alkyl.
 4. A compound of formula I according to claim 1 wherein n is one; and R₁ is C₁-C₄alkyl, C₂-C₄alkenyl; C₁-C₄haloalkyl; or C₁-C₂-dialkylamino; and R₂ is hydrogen and R₃ is C₃-C₄alkyl; allyl or cyclopropyl; and R₄ is hydrogen or methyl and R₅, R₆ and R₇ are each hydrogen; and R₈ is methyl or ethyl.
 5. A compound of formula I according to claim 1 wherein n is one; and R₁ is C₁-C₄alkyl, vinyl; C₁-C₄haloalkyl; or dimethylamino; and R₂ is hydrogen and R₃ is isopropyl; and R₄, R₅, R₆ and R₇ are each hydrogen; and R₈ is methyl.
 6. A compound of formula I according to claim 1 wherein A is optionally substituted heteroaryl consisting of one or two five to six membered rings containing one to four identical or different heteroatoms selected from oxygen, nitrogen and sulfur.
 7. A compound of formula I according to claim 1, wherein R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each independently hydrogen or methyl; and X is oxygen, sulfur or —NR₁₈—, wherein R₁₈ is hydrogen or methyl; and A is phenyl, naphthyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, benzothiophenyl, benzofuranyl, benzimidazolyl, benzthiazolyl, benzoxazolyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₃-C₈-cycloalkyl, C₃-C₈-cycloalkyl-C₁-C₄-alkyl, phenyl, phenyl-C₁-C₄-alkyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₃-C₈-alkenyloxy; C₃-C₈-alkynyloxy; C₁-C₈-alkoxy-C₁-C₄-alkyl; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; C₁-C₈-alkylsulfonyl; formyl; C₂-C₈-alkanoyl; hydroxy; halogen; cyano; nitro; amino; C₁-C₈-alkylamino; C₁-C₈-dialkylamino; carboxy; C₁-C₈-alkoxycarbonyl; C₁-C₈-alkenyloxycarbonyl or C₁-C₈-alkynyloxycarbonyl.
 8. A compound of formula I according to claim 1, wherein R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each hydrogen; and X is oxygen, sulfur or —NH—; or A is phenyl, naphthyl, thienyl, pyridyl, pyrimidinyl, triazinyl or quinolyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl, C₂-C₈-alkenyl wherein the hydrogens of all the preceding substituents may be in turn optionally substituted by one or several same or different halogens; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl.
 9. A compound of formula I according to claim 1, wherein R₉, R₁₀, R₁₄, R₁₅, R₁₆, R₁₇ are each hydrogen; and X is oxygen; and A is phenyl or pyridyl, each optionally substituted by 1 to 3 substituents selected from C₁-C₈-alkyl; C₁-C₈-haloalkyl; C₁-C₈-alkoxy; C₁-C₈halogenalkoxy; C₁-C₈-alkylthio; C₁-C₈-halogenalkylthio; halogen; cyano; nitro or C₁-C₈-alkoxycarbonyl.
 10. A process for the preparation of a compound of formula I according to claim 1, which comprises reacting a) an amino acid of formula II or a carboxy-activated derivative thereof

wherein R₁, n, R₂ and R₃ are as defined for formula I is reacted with an amine of formula III

wherein R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined for formula I optionally in the presence of a base and optionally in the presence of a diluting agent, or b) an amino acid derivative of formula VI

wherein R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and R₁₁ are as defined for formula I with a sulfonyl halide or a sulfinyl halide of formula V

wherein R₁ and n are as defined for formula I and X is halide, preferentially chlorine or bromine, or c) a phenol of formula VII

wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇ and R₈ are as defined for formula I with a compound of formula VIII

wherein R₉, R₁₀ and R₁₁ are as defined for formula I and Y is a leaving group like a halide such as a chloride or bromide or a sulfonic ester such as a tosylate, mesylate or triflate.
 11. A process for the preparation of a compound of formula Ia

wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and A are defined in claim 1 for formula I which comprises reacting a compound of formula IX

wherein R₁, n, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀ and A are defined for formula I with hydrogen.
 12. A composition for controlling and protecting against phytopathogenic microorganisms, comprising a compound of formula I according to claim 1 as active ingredient together with a suitable carrier.
 13. A method of controlling and preventing an infestation of crop plants by phytopathogenic microorganisms, preferably fungal organisms, which comprises the application of a compound of formula I according to claim 1 as active ingredient to the plant, to parts of plants or to the locus thereof. 